Blood processing systems and methods that employ an in-line, flexible leukofilter

ABSTRACT

Systems and methods separate pump the blood cells through an in-line leukofilter to a blood cell storage container. The leukofilter has a filtration medium enclosed within a flexile housing. The systems and methods can employ a fixture to restrain expansion of the flexible filter housing during operation of the pump.

RELATED APPLICATIONS

This application is a continuation of U.S. application Ser. No.09/976,833, filed Oct. 13, 2001, now U.S Pat. No. 6,709,412 and entitled“Blood Separation Systems and Methods that Employ an In-Line LeukofilterMounted in a Restraining Fixture,” which is a continuation-in-part ofU.S. patent application Ser. No. 09/389,504, filed Sep. 3, 1999, nowU.S. Pat. No. 7,041,076 and entitled “Blood Separation Systems andMethods Using a Multiple Function Pump Station to Perform DifferentOn-Line Processing Tasks,” which is incorporated herein by reference.

FIELD OF THE INVENTION

This invention relates to systems and methods for processing andcollecting blood, blood constituents, or other suspensions of cellularmaterial.

BACKGROUND OF THE INVENTION

Today people routinely separate whole blood, usually by centrifugation,into its various therapeutic components, such as red blood cells,platelets, and plasma.

Conventional blood processing methods use durable centrifuge equipmentin association with single use, sterile processing systems, typicallymade of plastic. The operator loads the disposable systems upon thecentrifuge before processing and removes them afterwards.

Conventional blood centrifuges are of a size that does not permit easytransport between collection sites. Furthermore, loading and unloadingoperations can sometimes be time consuming and tedious.

In addition, a need exists for further improved systems and methods forcollecting blood components in a way that lends itself to use in highvolume, on line blood collection environments, where higher yields ofcritically needed cellular blood components, like plasma, red bloodcells, and platelets, can be realized in reasonable short processingtimes.

The operational and performance demands upon such fluid processingsystems become more complex and sophisticated, even as the demand forsmaller and more portable systems intensifies. The need therefore existsfor automated blood processing controllers that can gather and generatemore detailed information and control signals to aid the operator inmaximizing processing and separation efficiencies.

SUMMARY OF THE INVENTION

The invention provides systems and methods for processing blood andblood constituents that lend themselves to portable, flexible processingplatforms equipped with straightforward and accurate control functions.

One aspect of the invention provides blood processing systems andmethods comprising a blood processing set that includes a source ofblood cells and a blood component collection flow channel coupled to thesource of blood cells. The blood component collection flow channelincludes a blood cell storage container and an in-line filter to removeleukocytes from the blood cells before entering the blood cell storagecontainer. The in-line filter includes a leukocyte removal filter mediumand first and second flexible housings. The blood processing systemfurther includes a pump station adapted to be placed into communicationwith the blood component collection flow channel to pump blood into theblood cell storage container through the in-line filter, and includes aseparate restraining structure contacting an outer surface of each ofthe first and second flexible housings to restrain the outward expansionof the first and second flexible housings as a result of pressureapplied during operation of the pump station.

In one embodiment, the source of blood cells includes a donor flowchannel including a blood separation device to separate blood cells fromdonor whole blood. Other features and advantages of the inventions areset forth in the following specification and attached drawings.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a perspective view of a fluid processing system that embodiesfeatures of the invention, with the doors to the centrifuge station andpump and valve station being shown open to accommodate mounting of afluid processing set;

FIG. 2 is a perspective view of the system shown in FIG. 1, with thedoors to the centrifuge station and pump and valve station being shownclosed as they would be during fluid processing operations;

FIG. 3 is a schematic view of a representative blood processing circuitformed by the fluid processing set shown in FIGS. 1 and 2;

FIG. 4 is a perspective view of a blood processing chamber andassociated fluid conveying umbilicus that form a part of the fluidprocessing set shown in FIGS. 1 and 2;

FIG. 5 is an exploded top perspective view of the of a two-part moldedcentrifugal blood processing container, which can form a part of thefluid processing set used in association with the device shown in FIGS.1 and 2;

FIG. 6 is a bottom perspective view of the molded processing containershown in FIG. 5;

FIG. 7 is a side section view of the molded processing container shownin FIG. 5, after connection of an umbilicus;

FIG. 8 is a side section view of a three-part molded centrifugal bloodprocessing container which can form a part of the fluid processing setused in association with the device shown in FIGS. 1 and 2;

FIG. 9 is a top view of the molded processing container shown in FIG. 5,showing certain details of the separation channel;

FIG. 10 is an exploded perspective view of the centrifuge station andassociated centrifuge assembly of the device shown in FIGS. 1 and 2;

FIG. 11 is an enlarged exploded perspective view of the centrifugeassembly shown in FIG. 10;

FIG. 12 is a perspective view of the centrifuge assembly fully assembledand housed in the centrifuge station of the device shown in FIGS. 1 and2, with the blood processing chamber and associated umbilicus alsomounted on the centrifuge assembly for use;

FIG. 13 is a perspective view of the rotor plate that forms a part ofthe centrifuge assembly shown in FIGS. 10 to 12, showing the latchassembly which releasably secures the processing chamber to thecentrifuge assembly, the latch assembly being shown in its chamberretaining position;

FIG. 14 is a side section view of the rotor plate shown in FIG. 13,showing the components of the latching assembly as positioned when thelatch assembly is in its chamber retaining position;

FIG. 15 is a side section view of the rotor plate shown in FIG. 13,showing the components of the latching assembly as positioned when thelatch assembly is in its chamber releasing position;

FIGS. 16 to 18 are a series of perspective view of the centrifugestation of the device shown in FIGS. 1 and 2, showing the sequence ofloading the processing chamber and associated umbilicus on thecentrifuge assembly prior to use;

FIGS. 19 to 22 are a series of perspective view of the centrifugestation of the device shown in FIGS. 1 and 2, after loading theprocessing chamber and associated umbilicus on the centrifuge assembly,showing at ninety degree intervals the travel of the umbilicus to impartrotation to the processing chamber, as driven and restrained byumbilicus support members carried by the yoke;

FIG. 23 is a schematic view of a fluid processing circuit of the typeshown in FIG. 3, showing certain details of the arrangement of pumpsthat convey blood and fluid through the circuit;

FIGS. 24A and 24B are perspective views of a leukofilter that can form apart of the fluid process circuit shown in FIGS. 3 and 23, theleukofilter comprising a filter media enclosed between two flexiblesheets of plastic material, FIG. 24A showing the leukofilter in anexploded view and FIG. 24B showing the leukofilter in an assembled view;

FIGS. 25A and 25B are perspective views of the leukofilter shown in FIG.24B in association with a fixture that retains the leukofilter duringuse, FIG. 25A showing the leukofilter being inserted into an openedfixture and FIG. 25B showing the leukofilter retained for use within aclosed fixture;

FIG. 26 is a perspective view of a device of a type of shown in FIGS. 1and 2, with the lid of the device closed to also reveal the location ofvarious components and a leukofilter holder carried on the exterior ofthe lid;

FIG. 27 is a partial perspective view of a side of the base of a deviceof a type shown in FIGS. 1 and 2, showing a holder for supporting theleukofilter retaining fixture shown in FIGS. 25A and 25B during fluidprocessing operations;

FIG. 28 is a view of one side of the leukofilter retaining fixture of atype shown in FIGS. 25A and 25B, showing a mounting bracket that can beused to secure the leukofilter either to the lid-mounted receptacleshown in FIG. 26 or the base-mounted holder shown in FIG. 27; and

FIG. 29 is an exploded perspective view of a cassette, which can form apart of the processing set used in association with the processingdevice shown in FIGS. 1 and 2, and the pump and valve station on theprocessing device, which receives the cassette for use.

The invention may be embodied in several forms without departing fromits spirit or essential characteristics. The scope of the invention isdefined in the appended claims, rather than in the specific descriptionpreceding them. All embodiments that fall within the meaning and rangeof equivalency of the claims are therefore intended to be embraced bythe claims.

DESCRIPTION OF THE PREFERRED EMBODIMENTS

FIG. 1 shows a fluid processing system 10 that embodies the features ofthe invention. The system 10 can be used for processing various fluids.

The system 10 is particularly well suited for processing whole blood andother suspensions of biological cellular materials. Accordingly, theillustrated embodiment shows the system 10 used for this purpose.

I. System Overview

The system 10 includes three principal components. These are: (i) aliquid and blood flow set 12 (shown schematically in FIG. 3); (ii) ablood processing device 14 (see FIGS. 1 and 2), which interacts with theflow set 12 to cause separation and collection of one or more bloodcomponents; and (iii) a controller 16 carried on board the device 14,which governs the interaction to perform a blood processing andcollection procedure selected by the operator.

A. The Processing Device and Controller

The blood processing device 14 and controller 16 are intended to bedurable items capable of long term use. In the illustrated and preferredembodiment, the blood processing device 14 and controller 16 are mountedinside a portable housing or case 36. The case 36 presents a compactfootprint, suited for set up and operation upon a table top or otherrelatively small surface. The case 36 is also intended to be transportedeasily to a collection site.

The case 36 includes a base 38 and a hinged lid 40, which opens for use(as FIG. 1 shows). In use, the base 38 is intended to rest in agenerally horizontal support surface. The lid 40 also closes fortransport (see FIG. 26).

The case 36 can be formed into a desired configuration, e.g., bymolding. The case 36 is preferably made from a lightweight, yet durable,plastic material.

The controller 16 carries out process control and monitoring functionsfor the system 10. The controller 16 comprises a main processing unit(MPU), which can comprise, e.g., a Pentium™ type microprocessor made byIntel Corporation, although other types of conventional microprocessorscan be used. The MPU can be mounted inside the lid 40 of the case 36.

Preferably, the controller 16 also includes an interactive userinterface 260, which allows the operator to view and comprehendinformation regarding the operation of the system 10. In the illustratedembodiment, the interface 260 includes an interface screen carried inthe lid 40, which displays information for viewing by the operator inalpha□numeric format and as graphical images.

Further details of the controller 16 can be found in Nayak et al, U.S.Pat. No. 6,261,065, which is incorporated herein by reference. Furtherdetails of the interface can be found in Lyle et al, U.S. Pat. No.5,581,687, which is also incorporated herein by reference.

As FIG. 26 shows, the lid 40 can be used to support other input/outputsto couple other external devices to the controller 16 or othercomponents of the device 14. For example, an ethernet port 50, or aninput 52 for a bar code reader or the like (for scanning informationinto the controller 16), or a diagnostic port 54, or a port 56 to becoupled to a pressure cuff 58 (see FIG. 3), or a system transducercalibration port 60, can all be conveniently mounted for access onexterior of the lid 40, or elsewhere on the case 36 of the device 14.

B. The Flow Set

The flow set 12 (see FIG. 3), is intended to be a sterile, single use,disposable item. Before beginning a given blood processing andcollection procedure, the operator loads various components of the flowset 12 in the case 36 in association with the device 14 (as FIGS. 1 and2 show). The controller 16 implements the procedure based upon presetprotocols, taking into account other input from the operator. Uponcompleting the procedure, the operator removes the flow set 12 fromassociation with the device 14. The portion of the set 12 holding thecollected blood component or components are removed from the case 36 andretained for storage, transfusion, or further processing. The remainderof the set 12 is removed from the case 36 and discarded.

The flow set 12 can take various forms. In the illustrated embodiment(see FIGS. 1 and 3), the flow set includes a blood processing chamber 18designed for use in association with a centrifuge. Accordingly, theprocessing device 14 includes a centrifuge station 20 (see FIG. 1),which receives the processing chamber 18 for use (see FIG. 12).

As FIG. 1 shows, the centrifuge station 20 comprises a compartment 21formed in the base 38. The centrifuge station 20 includes a door 22,which opens and closes the compartment 21. The door 22 opens (as FIG. 1shows) to allow loading of the processing chamber 18 into thecompartment 21. The door 22 closes (as FIG. 2 shows) to enclose theprocessing chamber 18 within the compartment 21 during operation.

The centrifuge station 20 rotates the processing chamber 18. Whenrotated, the processing chamber 18 centrifugally separates whole bloodreceived from a donor into component parts, e.g., red blood cells,plasma, and platelets.

In the illustrated embodiment, the set 12 also includes a fluid pressureactuated cassette 28 (see FIG. 29). The cassette 28 provides acentralized, programmable, integrated platform for all the pumping andvalving functions required for a given blood processing procedure. Inthe illustrated embodiment, the fluid pressure comprises positive andnegative pneumatic pressure. Other types of fluid pressure can be used.

The cassette 28 can take various forms. In a preferred embodiment (seeFIG. 29), the cassette 28 comprises an injection molded body 200 made ofa rigid medical grade plastic material. Flexible diaphragms 202,preferably made of flexible sheets of medical grade plastic, overlay thefront side and back sides of the cassette 28. The diaphragms are sealedabout their peripheries to the peripheral edges of the front and backsides of the cassette 28.

As FIG. 29 shows, the cassette 28 has an array of interior cavitiesformed on both the front and back sides The interior cavities definepneumatic pump stations (schematically designated PS in FIG. 3), whichare interconnected by a pattern of fluid flow paths (schematicallydesignated FP in FIG. 3) through an array of in line, pneumatic valves(schematically designated V in FIG. 3).

As FIGS. 1 and 29 show, the cassette 28 interacts with a pneumaticactuated pump and valve station 30, which is mounted in the lid of the40 of the case 36. The pump and valve station 30 includes a cassetteholder 216. A door 32 is hinged to move with respect to the cassetteholder 216 between an opened position, exposing the cassette holder 216(shown in FIG. 1) for loading and unloading the cassette 28, and aclosed position, enclosing the cassette 28 within the pump and valvestation 30 for use (shown in FIG. 2). The pump and valve station 30includes pneumatic actuator ports 204 (see FIG. 29) that apply positiveand negative pneumatic pressure upon the diaphragms of the cassette 28.The pneumatic pressures displace the diaphragms 202 with respect to thepump chambers and valves, to thereby direct liquid flow through thecassette 28.

Further details of the cassette 28 and the operation of the pump andvalve station 30 can be found in Nayak et al, U.S. Pat. No. 6,261,065,which is incorporated herein by reference.

Referred back to FIG. 3, the flow set 16 also includes an array of tubesand containers in flow communication with the cassette 28. Thearrangement of tubes and containers can vary according to the processingobjectives. The system 10 can be operated to collect red blood cells,plasma, red blood cells and plasma, and platelets.

In the illustrated embodiment, the flow set 16 is arranged to supportthe centrifugal collection of two units of red blood cells (about 360ml), and to filter the red blood cells to reduce the number ofleukocytes prior to storage. During this procedure, whole blood from adonor is centrifugally processed in the chamber 18 into red blood cells(in which a majority of the leukocytes resides) and a plasma constituent(in which a majority of the platelets resides). The plasma constituentis returned to the donor, while the targeted volume of red blood cellsis collected, filtered to reduce the population of leukocytes, andplaced into containers for storage mixed with a red blood cell storagesolution.

In this configuration (see FIG. 3), the flow set 16 includes a donortube 266 having an attached phlebotomy needle 268. The donor tube 266 iscoupled to a port of the cassette 28.

As FIG. 3 shows, a pressure cuff 58 is desirable used to enhance venousblood flow through the phlebotomy needle 268 during blood processing.The pressure cuff 58 is coupled to the pressure cuff port 56 on the lid40 (as previously described), and the pressure supplied to the cuff 58is desirably controlled by the controller 16. The controller 16 can alsooperate a vein pressure display 62 (see FIG. 26), which shows veinpressure at the pressure cuff 56.

An anticoagulant tube 270 is coupled to the phlebotomy needle 268. Theanticoagulant tube 270 is coupled to another cassette port. A container276 holding anticoagulant is coupled via a tube 274 to another cassetteport.

A container 288 holding saline is coupled via a tube 284 to anothercassette port.

The set 16 further includes tubes 290, 292, 294, which extend to anumbilicus 296. When installed in the processing station, the umbilicus296 links the rotating processing chamber 18 with the cassette 28without need for rotating seals. In a preferred embodiment, theumbilicus 296 is made from rotational-stress-resistant Hytrel®copolyester elastomers (DuPont). Further details of the construction ofthe umbilicus 296 will be provided later.

The tubes 290, 292, and 294 are coupled, respectively, to other cassetteports. The tube 290 conveys whole blood into the processing chamber 18.The tube 292 conveys plasma constituent from the processing chamber 18.The tube 294 conveys red blood cells from processing chamber 18.

A plasma collection reservoir 304 is coupled by a tube 302 to a cassetteport. The collection reservoir 304 is intended, in use, to serve as areservoir for the plasma constituent during processing prior to itsreturn to the donor.

A red blood cell collection reservoir 308 is coupled by a tube 306 to acassette port. The collection reservoir 308 is intended, in use, toreceive red blood cells during processing for storage.

Two red blood cell storage containers 307 and 309 are coupled by a tube311 to another cassette port. A leukocyte reduction filter 313 iscarried in line by the tube 311. During processing, red blood cells aretransferred from the red blood cell collection reservoir 308 through thefilter 313 into the storage containers 307 and 309.

A container 208 holding a red blood cell storage or additive solution iscoupled via a tube 278 to another cassette port. The red blood cellstorage solution is metered into the red blood cells as they areconveyed from the container 308, through the filter 313, into thestorage containers 307 and 309. Further details of this aspect of thecollection process will be described later.

A whole blood reservoir 312 is coupled by a tube 310 to a cassette port.The collection container 312 is intended, in use, to serve as areservoir for whole blood during processing.

In the illustrated embodiment, the set 16 further includes a fixture 338(see FIG. 4) to hold the tubes 292 and 294 in viewing alignment with anoptical sensing station 332 in the base 36 (see FIG. 12). The sensingstation 332 optically monitors the presence or absence of targeted bloodcomponents (e.g., platelets and red blood cells) conveyed by the tubes292 and 294. The sensing station 332 provides output reflecting thepresence or absence of such blood components. This output is conveyed tothe controller 16. The controller 16 processes the output and generatessignals to control processing events based, in part, upon the opticallysensed events. Further details of the operation of the controller tocontrol processing events based upon optical sensing can be found inNayak et al, U.S. Pat. No. 6,261,065, which is incorporated herein byreference.

As FIG. 12 shows, the sensing station 332 is desirably located withinthe confines of the centrifuge station 20. This arrangement minimizesthe fluid volume of components leaving the chamber before monitoring bythe sensing station 332.

The fixture 338 gathers the tubes 292 and 294 in a compact, organized,side-by-side array, to be placed and removed as a group in associationwith the sensing station 332. In the illustrated embodiment, the fixture338 also holds the tube 290, which conveys whole blood into theprocessing chamber 18, even though no associated sensor is provided. Thefixture 338 serves to gather and hold all tubes 290, 292, and 294 thatare coupled to the umbilicus 296 in a compact and easily handled bundle.

The fixture 338 can be an integral part of the umbilicus 296, formed,e.g., by over molding. Alternatively, the fixture 338 can be aseparately fabricated part, which snap fits about the tubes 290, 292,and 294 for use.

As FIGS. 1 and 2 also show, the case 36 contains other componentscompactly arranged to aid blood processing. In addition to thecentrifuge station 20 and pump and valve station 30, already described,the case 36 includes a weigh station 238 and one or more trays 212 orhangers 248 for containers. The arrangement of these components in thecase 36 can vary.

In the illustrated embodiment, the weigh station 238 comprises a seriesof container hangers/weigh sensors 246 arranged along the top of the lid40. In use, the containers 304, 308, 312 are suspended on thehangers/weigh sensors 246.

The holding trays 212 comprise molded recesses in the base 38. The trays212 accommodate the containers 276 (containing anticoagulant) and 208(containing the red blood cell additive solution). In the illustratedembodiment, an additional swing-out side hanger 248 is also provided onthe side of the lid 40. The hanger 248 (see FIG. 2) supports thecontainer 288 (containing saline) during processing. Other swing outhangers 249 support the red blood cells storage containers 307 and 309.

In the illustrated embodiment, the tray 212 holding the container 276and the hanger 248 also include weigh sensors 246.

As blood or liquids are received into and/or dispensed from thecontainers during processing, the weigh sensors 246 provide outputreflecting weight changes over time. This output is conveyed to thecontroller 16. The controller 16 processes the incremental weightchanges to derive fluid processing volumes. The controller generatessignals to control processing events based, in part, upon the derivedprocessing volumes. Further details of the operation of the controllerto control processing events can be found in Nayak et al, U.S. Pat. No.6,261,065, which is incorporated herein by reference.

C. The Centrifugal Processing Chamber

FIGS. 5 to 7 show an embodiment of the centrifugal processing chamber18, which can be used in association with the system 10 shown in FIG. 1to perform the intended red blood cell collection procedure. In theillustrated embodiment, the processing chamber 18 is preformed in adesired shape and configuration, e.g., by injection molding, from arigid, biocompatible plastic material, such as a non□plasticized medicalgrade acrilonitrile-butadiene-styrene (ABS).

In one arrangement, the chamber 18 can be fabricated in two separatelymolded pieces; namely (as FIGS. 5 to 7 show), a base 388 and a lid 150.The base 388 includes a center hub 120. The hub 120 is surroundedradially by inside and outside annular walls 122 and 124. Between them,the inside and outside annular walls 122 and 124 define acircumferential blood separation channel 126. A molded annular wall 148closes the bottom of the channel 126.

The top of the channel 126 is closed by the separately molded, flat lid150 (which is shown separated in FIG. 5 for the purpose ofillustration). During assembly (see FIG. 7), the lid 150 is secured tothe top of the chamber 18, e.g., by use of a cylindrical sonic weldinghorn.

All contours, ports, channels, and walls that affect the bloodseparation process may be preformed in the base 388 in a single,injection molded operation, during which molding mandrels are insertedand removed through the open end of the base 388 (shown in FIG. 5). Thelid 150 comprises a simple flat part that can be easily welded to theopen end of the base 388 to close it after molding. Because all featuresthat affect the separation process are incorporated into one injectionmolded component, any tolerance differences between the base 388 and thelid 150 will not affect the separation efficiencies of the chamber 18.

The contours, ports, channels, and walls that are preformed in the base388 may create surfaces within the base 388 that do not readily permitthe insertion and removal of molding mandrels through a single end ofthe base 388. In this arrangement, the base 388 can be formed byseparate molded parts, either by nesting cup shaped subassemblies or twosymmetric halves.

Alternatively, molding mandrels can be inserted and removed from bothends of the base 388. In this arrangement (see FIG. 8), the chamber 18can be molded in three pieces; namely, the base 388, the lid 150 (whichcloses one end of the base 388 through which top molding mandrels areinserted and removed), and a separately molded insert 151 (which closesthe other end of the base 388 through which bottom molding mandrels areinserted and removed.

The contours, ports, channels, and walls that are preformed in the base388 can vary.

As seen in FIG. 9, in one arrangement, the inside annular wall 122 isopen between one pair of stiffening walls. The opposing stiffening wallsform an open interior region 134 in the hub 120, which communicates withthe channel 126. Blood and fluids are introduced from the umbilicus 296into and out of the separation channel 126 through this region 134.

In this embodiment (as FIG. 9 shows), a molded interior wall 136 formedinside the region 134 extends entirely across the channel 126, joiningthe outside annular wall 124. The wall 136 forms a terminus in theseparation channel 126, which interrupts flow circumferentially alongthe channel 126 during separation.

Additional molded interior walls divide the region 134 into threepassages 142, 144, and 146. The passages 142, 144, and 146 extend fromthe hub 120 and communicate with the channel 126 on opposite sides ofthe terminus wall 136. Blood and other fluids are directed from the hub120 into and out of the channel 126 through these passages 142, 144, and146.

The underside of the base 388 (see FIG. 7) includes a shaped receptacle179. The far end of the umbilicus 296 includes a shaped mount 178 (seeFIGS. 24 and 24A). The mount 178 is shaped to correspond to the shape ofthe receptacle 179. The mount 178 can thus be plugged into thereceptacle 179 (as FIG. 7 shows), to couple the umbilicus 296 in fluidcommunication with the channel 126.

The mount 178 is desirably made from a material that can withstandconsiderable flexing and twisting, to which the mount 178 can besubjected during use, e.g., Hytrel® 3078 copolyester elastomer (DuPont).The dimensions of the shaped receptacle 179 and the shaped mount 178 arepreferably selected to provide a tight, dry press fit, to thereby avoidthe need for solvent bonding or ultrasonic welding techniques betweenthe mount 178 and the base 388 (which can therefore be formed from anincompatible material, such as ABS plastic).

D. The Centrifuge Assembly

The centrifuge station 20 (see FIG. 10) includes a centrifuge assembly48. The centrifuge assembly 48 is constructed to receive and support themolded processing chamber 18 and umbilicus 296 for use.

As illustrated (see FIGS. 10 and 11), the centrifuge assembly 48includes a yoke 154 having bottom, top, and side walls 156, 158, 160.The yoke 154 spins on a bearing element 162 (FIG. 11) attached to thebottom wall 156. An electric drive motor 164 is coupled to the bottomwall 156 of the yoke 154, to rotate the yoke 154 about an axis 64. Inthe illustrated embodiment, the axis 64 is essentially horizontal (seeFIG. 1), although other angular orientations can be used.

A rotor plate 166 (see FIG. 11) spins within the yoke 154 about its ownbearing element 168, which is attached to the top wall 158 of the yoke154. The rotor plate 166 spins about an axis that is generally alignedwith the axis of rotation 64 of the yoke 154.

As FIG. 7 best shows, the top of the processing chamber 18 includes anannular lip 380, to which the lid 150 is secured. As FIG. 12 shows, therotor plate 166 includes a latching assembly 382 that removably gripsthe lip 380, to secure the processing chamber 18 on the rotor plate 166for rotation.

The configuration of the latching assembly 382 can vary. In theillustrated embodiment (see FIGS. 13 to 15), the latching assembly 382includes a latch arm 66 pivotally mounted on a pin in a peripheralrecess 68 in the rotor plate 166. The latch arm 66 pivots between aretaining position (shown in FIGS. 13 and 14) and a releasing position(shown in FIG. 15).

In the retaining position (see FIG. 14), an annular groove 70 on theunderside of the latch arm 66 engages the annular lip 380 of theprocessing chamber 18. The annular groove 70 on the latch arm 66coincides with an annular groove 71 that encircles the top interiorsurface of the rotor plate 166. The engagement of the lip 380 within thegroove 70/71 secures the processing chamber 18 to the rotor plate 166.

In the releasing position (see FIG. 15), the annular groove 70 is swungfree of engagement of the annular lip 380. This lack of engagementallows release of the processing chamber 18 from the remainder of thegroove 71 in the rotor plate 166.

In the illustrated embodiment, the latching assembly 382 includes asliding pawl 72 carried in a radial track 74 on the top of the rotorplate. In the track 74, the pawl 72 slides radially toward and away fromthe latch arm 66.

When the latch arm 66 is in its retaining position and the pawl 72 islocated in a radial position adjacent the latch arm 66 (see FIG. 14), afinger 76 on the pawl 72 slips into and engages a cam recess 78 in thelatch arm 66. The engagement between the pawl finger 76 and latch armcam recess 78 physically resists movement of the latch arm 66 toward thereleasing position, thereby locking the latch arm 66 in the retainingposition.

A spring 80 within the pawl 72 normally biases the pawl 72 toward thisradial position adjacent the latch arm 66, where engagement between thepawl finger 76 and latch arm cam recess 78 can occur. The latch arm 66is thereby normally held by the pawl 72 in a locked, retaining position,to hold the processing chamber 18 during use.

The pawl 72 can be manually moved against the bias of the spring 80radially away from its position adjacent the latch arm 66 (see FIG. 15).During this movement, the finger 76 on the pawl 72 slips free of the camrecess 78 in the latch arm 66. Free of engagement between the pawlfinger 76 and latch arm cam recess 78, the latch arm 66 is unlocked andcan be pivoted toward its releasing position. In the absence of manualforce against the bias of the spring 80, the pawl 72 returns by springforce toward its position adjacent the latch arm 66, to lock the latcharm 66 in the chamber retaining position.

In the illustrated embodiment (see FIG. 13), the top wall 158 of theyoke 154 carries a downward depending collar 82. The collar 82 rotatesin unison with the yoke 154, relative to the rotor plate 166. The collar82 includes a sidewall 84 that is continuous, except for a cut away oropen region 86.

As FIG. 17 best shows, the pawl 72 includes an upstanding key element88. The sidewall 84 of the collar 82 is located in the radial path thatthe key element 88 travels when the pawl 72 is manually moved againstthe bias of the spring 80 radially away from its position adjacent thelatch arm 66. The key element 88 abuts against the collar sidewall 84,to inhibit movement of the pawl 72 in this direction, unless the openregion 86 is aligned with the key element 88, as shown in FIGS. 13 and15. The open region 86 accommodates passage of the key element 88,permitting manual movement of the pawl 72 against the bias of the spring80 radially away from its position adjacent the latch arm 66, therebyallowing the latch arm 66 to pivot into its releasing position.

The interference between the collar sidewall 84 and the key element 88of the pawl 72 prevents manual movement of the pawl 72 away from thelatch arm 66, to unlock the latch arm 66 for movement into its releasingposition, unless the open region 86 and the key element 88 register. Theopen region 86 is aligned on the yoke 154 so that this registrationbetween the open region 86 and the key element 88 occurs only when therotor plate 166 is in a prescribed rotational position relative to theyoke 154. In this position (see FIG. 12), the sidewalls 160 of the yoke154 are located generally parallel to the plane of the opening to thecompartment, providing open access to the interior of the yoke 154. Inthis position (see FIG. 16), the processing chamber 18 can be freelyplaced without interference into the interior of the yoke 154, andloaded onto the rotor plate 166. In this position, uninhibited manualmovement of the pawl 72 allows the operator to pivot the latch arm 66into its releasing position, to bring the lid 150 of the chamber 18 intocontact against the rotor plate 166. Subsequent release of the pawl 72returns the pawl 72 toward the latch arm 66 and allows the operator tolock the latch arm 66 in its retaining position about the lip 380 of thechamber 18. The reverse sequence is accommodated when it is time toremove the processing chamber 18 from the rotor plate 166.

This arrangement makes possible a straightforward sequence of acts toload the processing chamber 18 for use and to unload the processingchamber 18 after use (see FIG. 16). As FIGS. 17 and 18 further show,easy loading of the umbilicus 296 is also made possible in tandem withfitting the processing chamber 18 to the rotor plate 166.

A sheath 182 on the near end of the umbilicus 296 fits into a preformed,recessed pocket 184 in the centrifuge station 20. The pocket 184 holdsthe near end of the umbilicus 296 in a non□rotating stationary positionaligned with the mutually aligned rotational axes 64 of the yoke 154 androtor plate 166.

The preformed pocket 184 is also shaped to accommodate loading of thefixture 338 at the same time the sheath 182 is inserted. The tubes 290,292, and 294 are thereby placed and removed as a group in associationwith the sensing station 332, which is located within the pocket 184.

Umbilicus support members 186 and 187 (see FIG. 12) are carried by aside wall 160 of the yoke 154. When the rotor plate 166 is located inits prescribed rotational position to enable easy loading of the chamber18 (see FIGS. 17 and 18), the support members 186 and 187 are presentedon the left side of the processing chamber 18 to receive the umbilicus296 at the same time that the sheath 182 and fixture 338 are manipulatedfor fitting into the pocket 184.

As FIG. 19 shows, one member 186 receives the mid portion of theumbilicus 296. The member 186 includes a surface 188 against which themid portion of the umbilicus 296 rests. The surface 188 forms a channelthat extends generally parallel to the rotational axis 64 and thataccommodates passage of the mid portion of the umbilicus 296. Thesurface 188 inhibits travel of the mid portion of the umbilicus 296 inradial directions toward and away from the rotational axis 64. However,the surface 188 permits rotation or twisting of the umbilicus 296 aboutits own axis.

The other member 187 receives the upper portion of the umbilicus 296.The member 187 includes a surface 190 against which the upper portion ofthe umbilicus 296 rests. The surface 190 forms a channel inclined towardthe top wall 158 of the yoke 154. The surface 190 guides the upperportion of the umbilicus 296 toward the recessed pocket 184, which islocated axially above the top wall 158 of the yoke 154, where theumbilicus sheath 182 and fixture 338 are fitted. Like the surface 188,the surface 190 inhibits travel of the upper portion of the umbilicus296 in radial directions toward and away from the rotational axis 64.However, like the surface 188, the surface 190 permits rotation ortwisting of the umbilicus 296 about its own axis.

Closing the centrifuge station door 20 positions a holding bracket 90 onthe underside of the door 20 in registry with the sheath 182 (see FIGS.17 and 18) Another holding bracket 92 on the underside of the door 20 ispositioned in registry with the fixture 338 when the door 20 is closed.A releasable latch 94 preferably holds the door shut during operation ofthe centrifuge assembly 48.

During operation of the centrifuge assembly 48 (see FIGS. 19 to 22), thesupport members 186 and 187 carry the umbilicus 296 so that rotation ofthe yoke 154 also rotates the umbilicus 296 in tandem about the yokeaxis. Constrained within the pocket 184 at its near end (i.e., at thesheath 182) and coupled to the chamber 16 at its far end (i.e., by themount 178), the umbilicus 296 twists upon the surfaces 188 and 190 aboutits own axis as it rotates about the yoke axis 64, even as the surfaces188 and 190 inhibit radial travel of the umbilicus relative to therotation axis 64. The twirling of the umbilicus 296 about its axis as itrotates upon the surfaces 188 and 190 at one omega with the yoke 154(typically at a speed of about 2250 RPM) imparts a two omega rotation tothe processing chamber 18 secured for rotation on the rotor plate 166.

The relative rotation of the yoke 154 at a one omega rotational speedand the rotor plate 166 at a two omega rotational speed, keeps theumbilicus 296 untwisted, avoiding the need for rotating seals. Theillustrated arrangement also allows a single drive motor 164 to impartrotation, through the umbilicus 296, to the mutually rotating yoke 154and processing chamber 18 carried on the rotor plate 166. Furtherdetails of this arrangement are disclosed in Brown et al U.S. Pat. No.4,120,449, which is incorporated herein by reference.

The umbilicus 296 can stretch in response to the rotational forces itencounters. The dimensions of a given umbilicus 296 are also subject tonormal manufacturing tolerances. These factors affect the flight radiusof the umbilicus 296 during use; as well as the stress encountered bythe mount 178 at the far end of the umbilicus 296, which serves as thetwo omega torque transmitter to drive the processing chamber 18; as wellas the lateral loads acting on the centrifuge and motor bearings.

As FIGS. 19 to 22 show, the support members 186 and 187 on the yokeserve to physically confine the flight of the umbilicus 296 between theone omega region (mid portion) and two omega region (far end portion),as well as between the one omega region (mid portion) and zero omegaregion (near end portion) of the umbilicus 296. By confining theumbilicus 296 to a predefined radial distance from and radialorientation with respect to the rotational axis of the centrifugeassembly 48, the support members 186 and 187 serve to attenuate thefactors that can affect umbilicus performance and endurance.

The support members 186 and 187 make possible a bearing-less umbilicusassembly with no moving parts, while leading to reduced stress at thetwo omega torque region, where stresses tend to be greatest. Thesurfaces 188 and 190 of the support members 186 and 187 can be formedand oriented to accommodate rotation of the umbilicus 296 and thedriving of the processing chamber 18 in either clockwise orcounterclockwise directions.

In the illustrated embodiment, the surfaces 188 and 190 of the supportmembers 186 and 187 are preferably fabricated from a low frictionmaterial, to thereby eliminate the need for external lubrication orrotating bearings on the umbilicus 296 itself. The material used can,e.g., comprise Teflon® polytetrafluoroethylene material (DuPont) or anultra high molecular weight polyethylene. Made from such materials, thesurfaces 188 and 190 minimize umbilicus drive friction and the presenceof particulate matter due to umbilicus wear.

In a representative embodiment (see FIG. 4), the umbilicus 296 desirablycomprises a two layer co-extruded assembly. The interior or core layer96 desirably comprises Hytrel® 4056 copolyester elastomer (DuPont). Theoutside layer 98 desirably comprises Hytrel® 3078 copolyester elastomer(DuPont). The outside layer 98 may comprise a relatively thin extrusion,compared to the core layer 96.

In this arrangement, the outside layer 98 of Hytrel® 3078 copolyesterelastomer serves as a compatible interface to accommodate over-moldingof the zero omega sheath 182 and the two omega mount 178, which maycomprise the same Hytrel® 3078 material or an otherwise compatiblematerial. Absent material compatibility, solvents (e.g., methylenechloride) or other forms of surface treatment may be required tofacilitate a robust bond between these elements and the umbilicus.Hytrel® 3078 material is desired for the sheath 182, and the mount 178because it can withstand considerable flexing and twisting forces, towhich these regions of the umbilicus are subjected during use.

The core layer 96 of Hytrel® 4056 copolyester elastomer can be readilysolvent bonded to conventional flexible medical grade polyvinyl tubing,from which the tubes 290, 292, and 294 are desirably made.

II. Double Red Blood Cell Collection Procedure

Use of the set 12 in association with the device 14 and controller 16 toconduct a typical double unit red blood cell collection procedure willnow be described for illustrative purposes.

A. The Cassette

The cassette 28 used for a procedure of this type desirably includesdual pneumatic pump chambers PP3 and PP4 (see FIG. 23) which areoperated by the controller 16 in tandem to serve as a general purpose,donor interface pump. The dual donor interface pump chambers PP3 and PP4work in parallel. One pump chamber draws fluid, while the other pumpchamber expels fluid. The dual pump chambers PP3 and PP4 therebyalternate draw and expel functions to provide a uniform outlet flow.

The cassette 28 also desirably includes a pneumatic pump chamber PP5,which serves as a dedicated anticoagulant pump, to draw anticoagulantfrom the container 276 and meter the anticoagulant into the blood drawnfrom the donor.

The cassette 28 also desirably includes a pneumatic pump chamber PP1that serves as a dedicated in-process whole blood pump, to convey wholeblood from the reservoir 312 into the processing chamber 18. Thededicated function of the pump chamber PP1 frees the donor interfacepump chambers PP3 and PP4 from the added function of supplying wholeblood to the processing chamber 18. Thus, the in-process whole bloodpump chamber PP1 can maintain a continuous supply of blood to theprocessing chamber 18, while the donor interface pump chambers PP3 andPP4 operate in tandem to simultaneously draw and return blood to thedonor through the single phlebotomy needle. Processing time is therebyminimized.

The cassette 28 also desirably includes a pneumatic pump chamber PP2that serves as a plasma pump, to convey plasma from the processingchamber 18. The ability to dedicate separate pumping functions providesa continuous flow of blood into and out of the processing chamber 18, aswell as to and from the donor.

B. Capacitive Flow Sensing

The controller 16 desirably includes means for monitoring fluid flowthrough the pump chambers PP1 to PP5. In the illustrated embodiment, thepump and valve station 30 carries electrode circuits 206 associated witheach pump chamber PP1 to PP5. The electrode circuits 206 can be located,e.g., within the pneumatic actuator ports 204 in the pump and valvestation 30 (see FIG. 29) that apply negative and positive pressure tothe diaphragms to thereby draw fluid into the chambers PP1 to PP5 andexpel fluid from the chambers PP1 to PP5. The electrode circuits 206 arecoupled to an electrical source and are in electrical conductive contactwith fluids within their respective pump chambers PP1 and PP5.

The passage of electrical energy through each electrode circuit 206creates an electrical field within the respective pump chamber PP1 toPP5. Cyclic deflection of the diaphragm associated with a given pumpchamber to draw fluid into and expel fluid from the pump chamber PP1 toPP5 changes the electrical field, resulting in a change in totalcapacitance of the circuit through the electrode. Capacitance increasesas fluid is draw into the pump chamber PP1 to PP5, and capacitancedecreases as fluid is expelled from pump chamber PP1 to PP5.

In the arrangement, the electrode circuits 206 each includes acapacitive sensor (e.g., a Qprox E2S). The capacitive sensor registerschanges in capacitance for the electrode circuit 206 for each pumpchamber PP1 to PP5. The capacitance signal for a given electrode circuit206 has a high signal magnitude when the pump chamber is filled withliquid, has a low signal magnitude signal when the pump chamber is emptyof fluid, and has a range of intermediate signal magnitudes when thediaphragm occupies intermediate positions.

At the outset of a blood processing procedure, the controller 16 cancalibrate the difference between the high and low signal magnitudes foreach sensor to the maximum stroke volume of the respective pump chamber.The controller 16 can then relate the difference between sensed maximumand minimum signal values during subsequent draw and expel cycles tofluid volume drawn and expelled through the pump chamber. The controller16 can sum the fluid volumes pumped over a sample time period to yieldan actual flow rate.

The controller 16 can compare the actual flow rate to a desired flowrate. If a deviance exists, the controller 16 can vary pneumaticpressure pulses delivered to the actuators for the pump chambers PP1 toPP5 to minimize the deviance.

The controller 16 can also operate to detect abnormal operatingconditions based upon the variations in the electric field and togenerate corresponding alarm outputs. The controller 16 can, e.g.,monitor for an increase in the magnitude of the low signal magnitudeover time. The increase in magnitude reflects the presence of air insidea pump chamber.

For example, the controller 16 can generate a derivative of the signaloutput of the sensor 426. Changes in the derivative, or the absence of aderivative, reflects a partial or complete occlusion of flow through thepump chamber PP1 to PP5. The derivative itself also varies in a distinctfashion depending upon whether the occlusion occurs at the inlet oroutlet of the pump chamber PP1 to PP5.

1. Monitoring Vein Flow Conditions

By using capacitive sensing and by also counting pump strokes (i.e., theapplication of negative pressure upon the diaphragm of a given pumpchamber to draw fluid into the chamber), the controller 16 can alsomonitor vein flow conditions, and, in particular, assess and respond toreal or potential vein occlusion conditions.

When blood is pumped from the donor, the donor's vein may showdifficulties in keeping up with the commanded draw rate that operationof the donor pump chambers PP3/PP4 imposes. In the case of restrictedblood flow from the donor, the donor pumps PP3 and PP4 do not fillproperly in response to the commanded sequence of pump strokes. Thecontroller 16 attempts to assess and mediate blood supply interruptionsdue to vein problems before generating a vein occlusion alarm, whichsuspends processing.

For example, the controller 16 can count the number of consecutiveattempted pump strokes for which no blood flow into the pump chambersPP3 and PP4 occurs (which blood flow or absence of blood flow can bedetected by capacitive sensing, as above described). A potential donordraw occlusion condition can be deemed to occur when a prescribed number(e.g., 3) of consecutive incomplete fill donor pump strokes takes place.

When a potential donor draw occlusion condition is detected, thecontroller 16 attempts to rectify the condition by increasing pressureof the pressure cuff 58 and/or decreasing the commanded draw rate,before generating a processing-halting vein occlusion alarm.

More particularly, in a representative implementation, when a donor drawocclusion condition is detected, the controller 16 executes a potentialdraw occlusion condition function (in shorthand, the “PotentialOcclusion Function”). The Potential Occlusion Function first suspendsthe draw for a period of time (e.g. upwards to 20 seconds, and desirablyabout 10 seconds) to rest the vein. While the vein rests, the controller16 also increases the pressure cuff pressure by a preset increment(e.g., upwards to 25 mmHg, and desirably about 10 mmHg), unless cuffpressure, when adjusted, exceeds a prescribed maximum (e.g., upwards to100 mmHg, desirably about 70 mmHg). If the prescribed maximum cuffpressure condition exists, no incremental changes to the cuff pressureare made during the prescribed vein rest interval.

After the prescribed vein rest interval, the Potential OcclusionFunction resets the attempted pump stroke counter to zero and resumesthe draw cycle. The controller 16 monitors the initial series ofconsecutive pump strokes during the resumed draw cycle, up to a firstthreshold number of pump strokes (e.g., 5). The magnitude of the firstthreshold number is larger that the number of consecutive incompletefill donor pump strokes (i.e., 3) that indicate a potential donor drawocclusion condition. The magnitude of the first threshold number isselected to accurate assess, after a potential donor draw occlusioncondition arises, whether a true donor draw occlusion exists. In theillustrated embodiment, if within the first five pump strokes (orwhatever the first threshold number is), three consecutive incompletefill donor pump strokes take place, the controller 16 assumes that atrue donor draw occlusion exists, and thus generates an occlusion alarm.With the generation of an occlusion alarm, the controller 16 suspendsprocessing, until the operator can establish that it is safe to resume.

If within the first threshold number of pump strokes, three consecutiveincomplete fill donor pump strokes do not take place, the controller 16assumes that a true vein occlusion may not exist, and that the potentialoccluded flow condition was either transient, or at least capable ofcorrection short of suspending the procedure. In this event, thePotential Occlusion Function allows the resumed draw cycle to continuebeyond the first threshold number of pump strokes up to a secondthreshold number of pump strokes (e.g., 20 to 100, and desirable about50).

If at any time between the first threshold number of pump strokes andthe second threshold number of pump strokes, three consecutiveincomplete fill donor pump strokes take place, the Potential OcclusionFunction institutes another vein rest interval (e.g. upwards to 20seconds, and desirably about 10 seconds). While the vein rests, thePotential Occlusion Function also again increases the pressure cuffpressure by a preset increment (e.g., upwards to 25 mmHg, and desirablyabout 10 mmHg). While the vein rests, the Potential Occlusion Functionalso lowers the draw rate by a preset decrement (e.g., upwards to 20ml/min, and desirably about 10 ml/min). If the draw rate, when lowered,is less than a prescribed minimum draw rate (e.g., 70 to 90 ml/min), thecontroller 16 generates an occlusion alarm. Otherwise, the PotentialOcclusion Function resets the attempted pump stroke counter to zero, andresumes the draw cycle at the increased cuff pressure and decreased drawrate.

The controller 16 again monitors the initial series of consecutive pumpstrokes during the resumed draw cycle, up to the first threshold numberof pump strokes (e.g., 5). If within the first threshold number of pumpstrokes, three consecutive incomplete fill donor pump strokes takeplace, the controller 16 assumes that a true donor draw occlusionexists, and thus generates an occlusion alarm and also suspendsprocessing.

However, if within the first threshold number of pump strokes, threeconsecutive incomplete fill donor pump strokes do not take place, thecontroller 16 allows the resumed draw cycle to continue beyond the firstthreshold number of pump strokes up to the second threshold number ofpump strokes (e.g., 20 to 100, and desirable about 50). If at any timebetween the first threshold number of pump strokes and the secondthreshold number of pump strokes, three consecutive incomplete filldonor pump strokes take place, the Potential Occlusion Function againinstitutes another vein rest interval (e.g. upwards to 20 seconds, anddesirably about 10 seconds). While the vein rests, the PotentialOcclusion Function also again increases the pressure cuff pressure by apreset increment (e.g., upwards to 25 mmHg, and desirably about 10mmHg). While the vein rests, the Potential Occlusion Function also againlowers the draw rate by a preset decrement (e.g., upwards to 20 ml/min,and desirably about 10 ml/min), unless the draw rate, when lowered, isless than a prescribed minimum draw rate (e.g., 70 to 90 ml/min), inwhich case the controller 16 generates an occlusion alarm. Otherwise,the Potential Occlusion Function resets the attempted pump strokecounter to zero, and resumes the draw cycle at the increased cuffpressure and decreased draw rate.

The controller 16 continues to repeat the steps of the PotentialOcclusion Function, using the first and second pump stroke numberthresholds to gage whether a true vein occlusion exists, and eithergenerating an occlusion alarm if it does, or continuing to attemptremedial action (by increasing cuff pressure and/or decreasing drawrate), or cancelling the potential donor draw occlusion condition whenthree consecutive incomplete fill donor pump strokes are not observedduring either the first or second threshold periods following apotential donor occlusion condition.

If no three consecutive incomplete fill donor pump strokes take placewithin the second threshold number of strokes following a potentialdonor draw occlusion condition, the controller 16 assumes that a truevein occlusion does not exist. The draw cycle continues, and thecontroller 16 continues to count pump strokes. If the prescribed number(e.g., 3) of consecutive incomplete fill donor pump strokes subsequentlytakes place, the controller 16 assumes that this event is unrelated toany previous occlusion event condition, and generates a new potentialdonor draw occlusion condition, executing the Potential OcclusionFunction from the start.

It should be appreciated that the Potential Occlusion Function, as justdescribed, can be used with any blood processing device that has meansfor detecting when a draw blood pumping command does not result in bloodflow through the pump.

C. Blood Processing Cycles

Prior to undertaking the double unit red blood cell collectionprocedure, as well as any blood collection procedure, the controller 16conducts an appropriate integrity check of the cassette 28, to determinewhether there are any leaks in the cassette 28. Once the cassetteintegrity check is complete and no leaks are found, the controller 16begins the desired blood collection procedure.

In general, using the processing chamber shown in FIG. 9), whole bloodis introduced into and separated within the processing chamber 18 as itrotates. As the processing chamber 18 rotates (arrow R in FIG. 9), theumbilicus 296 conveys whole blood into the channel 126 through thepassage 146. The whole blood flows in the channel 126 in the samedirection as rotation (which is counterclockwise in FIG. 9).Alternatively, the chamber 18 can be rotated in a direction opposite tothe circumferential flow of whole blood, i.e., clockwise, but rotationin the same direction as circumferential blood flow is preferred.

The whole blood separates as a result of centrifugal forces. Red bloodcells are driven toward the high□G wall 124, while lighter plasmaconstituent is displaced toward the low□G wall 122. In this flowpattern, a dam 384 projects into the channel 126 toward the high-G wall124. The dam 384 prevents passage of plasma, while allowing passage ofred blood cells into a channel 386 recessed in the high-G wall 124. Thechannel 386 directs the red blood cells into the umbilicus 296 throughthe radial passage 144. The plasma constituent is conveyed from thechannel 126 through the radial passage 142 into umbilicus 296.

1. Collection Cycle

During a typical collection cycle of the double unit red blood cellcollection procedure, whole blood drawn from the donor is processed tocollect two units of red blood cells, while returning plasma to thedonor. The donor interface pumps PP3/PP4 in the cassette, theanticoagulant pump PS in the cassette, the in-process pump PP1 in thecassette, and the plasma pump PP2 in the cassette are pneumaticallydriven by the controller 16, in conjunction with associated pneumaticvalves, to draw anticoagulated blood into the in-process container 312,while conveying the blood from the in-process container 312 into theprocessing chamber 18 for separation. This arrangement also removesplasma from the processing chamber into the plasma container 304, whileremoving red blood cells from the processing chamber into the red bloodcell container 308. This phase continues until an incremental volume ofplasma is collected in the plasma collection container 304 (as monitoredby a weigh sensor) or until a targeted volume of red blood cells iscollected in the red blood cell collection container (as monitored by aweigh sensor).

If the volume of whole blood in the in-process container 312 reaches apredetermined maximum threshold before the targeted volume of eitherplasma or red blood cells is collected, the controller 16 terminatesoperation of the donor interface pumps PP3/PP4 to terminate collectionof whole blood in the in-process container 312, while still continuingblood separation. If the volume of whole blood reaches a predeterminedminimum threshold in the in-process container 312 during bloodseparation, but before the targeted volume of either plasma or red bloodcells is collected, the controller 16 returns to drawing whole blood tothereby allow whole blood to enter the in-process container 312. Thecontroller toggles between these two conditions according to the highand low volume thresholds for the in-process container 312, until therequisite volume of plasma has been collected, or until the targetvolume of red blood cells has been collected, whichever occurs first.

2. Return Cycle

During a typical return cycle (when the targeted volume of red bloodcells has not been collected), the controller 16 operates the donorinterface pumps PP3/PP4 within the cassette 28, the in-process pump PP1within the cassette, and the plasma pump PP2 within the cassette, inconjunction with associated pneumatic valves, to convey anticoagulatedwhole blood from the in-process container 312 into the processingchamber 18 for separation, while removing plasma into the plasmacontainer 304 and red blood cells into the red blood cell container 308.This arrangement also conveys plasma from the plasma container 304 tothe donor, while also mixing saline from the container 288 in line withthe returned plasma. The in line mixing of saline with plasma raises thesaline temperature and improves donor comfort. This phase continuesuntil the plasma container 304 is empty, as monitored by the weighsensor.

If the volume of whole blood in the in-process container 312 reaches aspecified low threshold before the plasma container 304 empties, thecontroller 16 terminates operation of the in-process pump PP1 toterminate blood separation. The phase continues until the plasmacontainer 304 empties.

Upon emptying the plasma container 304, the controller 16 conductsanother collection cycle. The controller 16 operates in successivecollection and return cycles until the weigh sensor indicates that adesired volume of red blood cells have been collected in the red bloodcell collection container 308. The controller 16 terminates the supplyand removal of blood to and from the processing chamber, while operatingthe donor interface pumps PP3/PP4 in the cassette 28 to convey plasmaremaining in the plasma container 304 to the donor. The controller 16next operates the donor interface pumps PP3/PP4 in the cassette toconvey the blood contents remaining in the in-process container 312 tothe donor as well as convey saline to the donor, until a prescribedreplacement volume amount is infused, as monitored by a weigh sensor.

3. In-Line Leukofiltration Cycle

When the collection of red blood cells and the return of plasma andresidual blood components has been completed, the controller 16switches, either automatically or after prompting the operator, to anin-line leukofiltration cycle. During this cycle, red blood cells areremoved from the red blood cell collection reservoir 308 and conveyedinto the red blood cell storage containers 307 and 308 through theleukocyte removal filter 313. At the same time, a desired volume of redblood cell storage solution from the container 208 is mixed with the redblood cells.

In the first stage of this cycle, the controller 16 operates donorinterface pumps PP3/PP4 in the cassette to draw air from the red bloodcell storage containers 307 and 309, the filter 313, and the line 311,and to transfer this air into the red blood cell collection reservoir308. This stage minimizes the volume of air residing in the red bloodcell storage containers 307 and 309 before the leukocyte removal processbegins. The stage also provides a volume of air in the red blood cellcollection container 308 that can be used purge red blood cells from thefilter 313 into the red blood cell collection containers 307 and 309once the leukocyte removal process is completed.

In the next stage, the controller 16 operates the donor interface pumpsPP3/PP4 in the cassette 28 to draw a priming volume of storage solutionfrom the solution container 208 into the red blood cell collectionreservoir 308. This stage primes the tubing 278 between the container208 and the cassette 28, to minimize the volume of air pumped into thefinal red blood cell storage containers 307 and 309.

In the next stage, the controller 16 operates the donor interface pumpsPP3/PP4 in the cassette 28 to alternate pumping red blood cells from thered blood cell collection reservoir 308 into the red blood cellcollection containers 307 and 309 (through the filter 313), with pumpingof red blood cell storage solution from the container 208 into the redblood cell collection containers 307 and 309 (also through the filter313). This alternating process mixes the storage solution with the redblood cells. The controller 16 counts the pneumatic pump strokes for redblood cells and the storage solution to obtain a desired ratio of redcell volume to storage solution volume (e.g., five pump strokes for redblood cells, followed by two pump strokes for storage solution, andrepeating the alternating sequence). This alternating supply of redblood cells and storage solution continues until the weigh scale for thered blood cell collection reservoir 308 indicates that the reservoir 308is empty.

When the red blood cell collection reservoir 308 is empty, thecontroller 16 operates the donor interface pumps PP3/PP4 to pumpadditional storage solution through the filter 313 and into the redblood storage containers 307 and 309, to ensure that a desired ratiobetween storage solution volume and red blood cell volume exists. Thisalso rinses residual red blood cells from the filter 313 into the redblood cell storage containers 307 and 309 to maximize post-filtrationpercent red blood cell recovery.

The controlled ratio of pump strokes for red blood cells and for storagesolution that the controller 16 achieves ensures that the storagesolution is always metered in at a constant ratio. Therefore, regardlessof the volume of red blood cells collected, the final red bloodcell/storage solution hematocrit can be constant.

The alternating supply of red blood cells and storage solution throughthe filter 313 eliminates the need to first drain the storage solutioninto the red blood cell collection reservoir 308, which lessens theoverall procedure time.

The alternating supply of red blood cells and storage solution throughthe filter 313 also eliminates the need to manually agitate a red bloodcell/storage solution mixture prior to leukofiltration. Due to densitydifferences, when concentrated red blood cells are added to apreservation solution, or vice versa, the preservation solution floatsto the top. Poorly mixed, high hematocrit, high viscosity red bloodcells lead to reduced flow rates during leukofiltration. Poorly mixed,high hematocrit, high viscosity red blood cell conditions can also leadto hemolysis. By alternating passage of red blood cells and storagesolution through the filter 313, mixing occurs automatically withoutoperator involvement.

The alternating supply of red blood cells and storage solution throughthe filter 313 also eliminates the need to gravity drain the red bloodcell product through the leukofilter 313. As a result, filtration canoccur in about half the time required for a gravity-drain procedure.

If desired, the controller 16 can monitor weight changes relating to thered blood cell collection reservoir 308 and the red blood cell storagecontainers 307 and 309, to derive a value reflecting the percent of redblood cells that are recovered after passage through the leukofilter313. This value can be communicated to the operator, e.g., on thedisplay screen of user the user interface.

The following expression can be used to derive the percent recoveryvalue:% Recovery=[(Bag A Vol+Bag B Vol)/RBC Vol+Adsol)]★100where:

Bag A Vol represents the volume of red blood cells collected thecontainer 307, calculated as follows:(Wt of Container 307 containing red blood cells (in g)−Container 307Tare)/1.062 g/ml

Bag B Vol represents the volume of red blood cells collected thecontainer 309, calculated as follows:(Wt of Container 309 containing red blood cells(in g)−Container 309Tare)/1.062 g/ml

RBC Vol represents the volume of red blood cells collected in the redblood cell collection reservoir 308, which the controller 16 determinesby weight sensing at the end of the procedure.

Adsol represents the volume of red blood cell storage solution added tothe during leukofiltration, which is determined by the controller 16 bycapacitive sensing during processing.

a. The Leukofilter

The leukofilter 313 can be variously constructed. In the embodimentillustrated in FIGS. 24A and 24B, the filter comprises a housing 100inclosing a filtration medium 102 that can comprise a membrane or bemade from a fibrous material. The filtration medium 102 can be arrangedin a single layer or in a multiple layer stack. If fibrous, the medium102 can include melt blown or spun bonded synthetic fibers (e.g., nylonor polyester or polypropylene), semi-synthetic fibers, regeneratedfibers, or inorganic fibers. If fibrous, the medium 102 removesleukocytes by depth filtration. If a membrane, the medium 102 removesleukocytes by exclusion.

The housing 100 can comprise rigid plastic plates sealed about theirperipheries. In the illustrated embodiment, the housing 100 comprisesfirst and second flexible sheets 104 of medical grade plastic material,such as polyvinyl chloride plasticized with di-2-ethylhexyl-phthalate(PVC-DEHP). Other medical grade plastic materials can be used that arenot PVC and/or are DEHP-free.

In the illustrated embodiment, a unitary, continuous peripheral seal 106(see FIG. 24B) is formed by the application of pressure and radiofrequency heating in a single process to the two sheets 104 andfiltration medium 102. The seal 106 joins the two sheets 104 to eachother, as well as joins the filtration medium 102 to the two sheets 104.The seal 106 integrates the material of the filtration medium 102 andthe material of the plastic sheets 104, for a reliable, robust,leak-proof boundary. Since the seal 106 is unitary and continuous, thepossibility of blood shunting around the periphery of the filtrationmedium 102 is eliminated.

The filter 313 also includes inlet and outlet ports 108. The ports 108can comprise tubes made of medical grade plastic material, likePVC-DEHP. In the embodiment shown in FIG. 24, the ports 108 compriseseparately molded parts that are heat sealed by radio frequency energyover a hole 109 formed in the sheets 104 (see FIG. 24B).

In the illustrated embodiment (as FIGS. 25A and 25B show), the filter313 is desirably placed within a restraining fixture 110 during use. Thefixture 110 restrains expansion of the flexible sheets 104 of the filterhousing 100 as a result of pressure applied by pumping red blood cellsthrough the filter 313. The fixture 110 keeps the total blood volume inthe filter 313 at a minimum through the filtration process, therebydecreasing filtration time, as well as increasing the red blood cellrecovery percentage following leukofiltration.

The fixture 110 can take various forms. In the illustrated embodiment,the fixture 110 comprises two plates 112 coupled by a hinge 114. Thefixture 110 can be placed in an open condition (as FIG. 25A shows) toreceive the filter 313 prior to leukofiltration, or to remove the filter313 following leukofiltration. The fixture 110 can also be placed in aclosed condition (as FIG. 25B shows) to sandwich the filter 313 betweenthe two plates 112. A releasably latch 116 holds the plates 112 in theclosed condition for use.

The plates 112 maintain a desired gap clearance, thereby restrainingexpansion of the filter 313 during use. The gap clearance is selected tomaintain a desired blood flow rate at a desired minimum blood volume.

The plates 112 desirably include indentations 118 in which the ports 108of the filter 313 rest in a non-occluded condition when the fixture 110is closed. The interior surfaces of the plates 112 may be roughed orscored with a finish to aid blood flow through the filter 313 when thefixture 110 is closed.

The fixture 110 can be made as a stand-alone item that can be separatelystored prior to use. It can be stored in association with the device 14during transport and prior to use, e.g., in a receptacle 128 formed onthe exterior of the lid 40 of the device 14 (see FIG. 26). The fixture110 can include a mounting bracket 130 (see FIG. 28) that, e.g.,slidably engages a mating mounting track 132, to hold the fixture 110 inthe receptacle 128 prior to use (shown in phantom lines in FIG. 26) orto secure the fixture 110 on the base 38 as leukofiltration is carriedout (see FIG. 27).

It should be appreciated that pump-assisted leukofiltration of red bloodcells, whole blood, or other blood cell products, wherein blood flowthrough a leukofilter is not driven strictly by gravity flow, can becarried out using manual or automated systems having configurationsdifferent than those shown in this Specification. For example, externalperistaltic or fluid actuated pumping devices can be used to transferwhole blood or manually processed blood products from separation bagsinto processing or storage containers through intermediateleukofiltration devices. It should also be appreciated that a filterrestraining fixture of the type shown in FIG. 24B can also be used inassociation with any pump-assisted leukofiltration system. It shouldalso be appreciated that a filter restraining fixture 110 can also beused in systems where blood flow through the leukofilter relies strictlyupon gravity flow.

The many features of the invention have been demonstrated by describingtheir use in separating whole blood into component parts for storage andblood component therapy. This is because the invention is well adaptedfor use in carrying out these blood processing procedures. It should beappreciated, however, that the features of the invention equally lendthemselves to use in other blood processing procedures.

For example, the systems and methods described, which make use of aprogrammable cassette in association with a blood processing chamber,can be used for the purpose of washing or salvaging blood cells duringsurgery, or for the purpose of conducting therapeutic plasma exchange,or in any other procedure where blood is circulated in an extracorporealpath for treatment.

Features of the invention are set forth in the following claims.

1. A blood processing system comprising a blood processing set includinga source of blood cells, and a blood component collection flow channelcoupled to the source of blood cells including a blood cell storagecontainer and an in-line filter to remove leukocytes from the bloodcells before entering the blood cell storage container, the in-linefilter including a leukocyte removal filter medium and first and secondflexible housings, a pump station adapted to be placed intocommunication with the blood component collection flow channel to pumpblood into the blood cell storage container through the in-line filter,and a separate restraining structure contacting an outer surface of eachof the first and second flexible housings to restrain the outwardexpansion of said housings under pressure applied during operation ofthe pump station.
 2. A blood processing system according to claim 1wherein the source of blood cells includes a donor flow channelincluding a blood separation device to separate blood cells from donorwhole blood.
 3. A blood processing system according to claim 1 whereinthe source of blood cells includes a donor flow channel including ablood separation device to separate blood cells from donor whole blood.4. A system according to claim 1 or 2 or 3 further comprising acontroller wherein the controller includes a function to derive a valuereflecting volume of blood cells present in the blood cell storagecontainer after passage through the filter as a percentage of volume ofblood cells conveyed to the filter.
 5. A system according to claim 1 or2 or 3 wherein the pump station includes a fluid pressure actuated pumpand an actuator to apply fluid pressure to the pump.
 6. A systemaccording to claim 1 or 2 or 3 wherein the blood cells comprise redblood cells.
 7. A method of processing blood comprising the steps ofproviding the blood processing system as defined in claim 1 or 2 or 3,pumping blood cells through the in-line filter, and conveying bloodcells from said filter into the blood cell storage container.
 8. A bloodprocessing system according to claim 1 wherein the leukocyte filtercomprises a fibrous filter medium.